Aryl Diazonium Salt‐Triggered Cyclization and Cycloaddition Reactions: Past,Present, and Future

Aryl diazonium salts occupy a privileged role in synthetic chemistry owing to their ready availability and versatile reactivity. While their applications in accessing diversely functionalized arene derivatives via denitrogenation‐coupling and reduction/addition reactions have been well recognized by practitioners in both academia and industry, recent renaissance in chemical transformations of retaining the key N₂‐unit has emerged as a powerful technique to construct various N‐heterocycles. This review covers the history and latest advances in cyclization and cycloaddition reactions using aryl diazonium salts as N₂‐annulation synthons. The scope, applications, and opportunities in exploring new chemical space by this sustainable strategy are summarized and discussed.     

Aromatic homolytic substitution using solid phase synthesis

Solid phase synthesis has been used to carry out intramolecular aromatic homolytic substitution with benzoimidazole precursors. The protocol attaches the radical precursors to the resins via the radical leaving groups (in the aromatic homolytic substitution). When the radical reactions are complete, the leaving group, unaltered starting material and reduced uncylised products remain attached to the resin, which facilitates easy separation of the cyclised products. Novel use of focussed microwave irradiation in solid phase radical reactions drastically shortens the reactions times. Tributylgermanium hydride has been used to replace the toxic and troublesome tributyltin hydride in the radical reactions.     

Alkynylation of N-tosylimines with aryl acetylenes promoted by ZnBr2 and N,N-diisopropylethylamine in acetonitrile

We found a suitable condition for the effective alkynylation of N-tosylimines with aryl acetylenes. The reaction of N-tosylimines and aryl acetylenes in the presence of ZnBr₂ and DIEA (N,N-diisopropylethylamine) in CH₃CN afforded the desired N-tosyl propargylamines in moderate to good yields.     

The metal-halogen exchange reaction between ortho-substituted aryl halides and Ph2CuLi · LiCN: scope and applicability for coupling reactions

Metal-halogen exchange between Ph₂CuLi · LiCN and ortho-substituted aryl iodides or bromides may be used to conveniently afford substituted metallated aryls which can subsequently undergo reaction with electrophiles.     

FeCl3-NaI mediated reactions of aryl azides with 3,4-dihydro-2H-pyran: a convenient synthesis of pyranoquinolines

The tetrahydroquinoline moiety is an important structural component of a number of natural products. The reaction of aryl azides with 3,4-dihydro-2H-pyran in the presence of FeCl₃-NaI affords the corresponding tetrahydroquinoline derivatives in an efficient manner. Most of the cyclizations exhibited cis selectivity.     

The vinylation of aryl iodides catalysed by Co, Rh and Ir complexes

The CoCl(PPh₃)₃, RhCl(PPh₃)₃, and IrClCO(PPh₃)₂ catalysed vinylation of aryl iodides proceeds to give cinnamates and stilbene in high yields.     

A novel MCM-41-supported sulfur palladium(0) complex catalyst for Sonogashira coupling reaction

A novel MCM-41-supported sulfur palladium(0) complex was conveniently prepared from commercially available and cheap γ-mercaptopropyltriethoxysilane via immobilization on MCM-41, followed by reacting with palladium chloride and then the reduction with hydrazine hydrate. This complex exhibited excellent performance in Sonogashira coupling reaction.     

An efficient palladium-catalyzed Heck coupling of aryl chlorides with alkenes

Catalyst system PdCl₂(PCy₃)₂/Cs₂CO₃ in dioxane was found to be the efficient catalyst system for Heck cross-coupling reactions of deactivated, neutral, and activated aryl chlorides with a variety of alkenes under mild conditions to afford selectively E-arylated alkenes in good to excellent yields.     

Structure‐Reactivity Relationships as Probes to Acetylcholinesterase Inhibition Mechanisms by Aryl Carbamates. I. Steady‐State Kinetics

From enzyme kinetics, 4‐nitrophenyl‐N‐substituted carbamates 1 are characterized as pseudo‐substrate inhibitors of acetylcholinesterase. However, the activity of the carbamyl enzyme does not recover in the presence of a competitive inhibitor, edrophonium. Therefore, carbamates 1 should be called as the “pseudo‐pseudo‐substrate” inhibitors of the enzyme. Moreover, the ‐logK_i, logk_c, and logk_i values are linearly correlated with Taft‐Ingold equation, log (k/k_o) = ρ*σ* + δ E_s. A three‐step AChE inhibition mechanism by carbamates 1 is proposed. The first step is the pre‐equilibrium protonations of carbamates 1 with ρ* value of ?1.4 from pK_a‐σ*‐correlation. The second step is the enzyme‐carbamates 1 tetrahedral intermediate formation from nucleophilic attack of the active site Ser200 on the protonated carbamates 1 . The ρ* value for the ‐logK_i‐σ*‐E_s‐correlation indicates that the true ρ* value for the second step is 0.5 [= ?0.9 ‐ (‐1.4)]. The δ value of 0.56 for the ‐logK_i‐σ*‐E_s‐correlation indicates that carbamates 1 with bulky substituents retarded the formation of enzyme‐inhibitor tetrahedral intermediates. The third step (k_c step) is the carbamylation step and is the carbamyl enzyme conjugate formation from the enzyme‐carbamates 1 tetrahedral intermediate. The ρ* value of 0.21 for the logk_c‐correlation indicates that the transition state for the carbamylation step is more negative charge than the enzyme‐carbamates 1 tetrahedral intermediate. Moreover, the k_c step is insensitive to substituent effects since there is a cancellation of electronic demands for bond‐making and bond‐breaking components, like S_N2 reactions. The δ value of 0.00 for the logk_c‐correlation indicates that the k_c step is independent of substituent steric effect. Therefore, the product of this step carbamyl enzyme conjugate is as crowded as the enzyme‐carbamates 1 tetrahedral intermediate and is likely bound to the leaving group, p‐nitrophenol.     

Nickel-promoted coupling of orthomanganated aryl ketones with alkenes as a route to indanols

Orthomanganated aryl ketones undergo NiBr₂(PPh₃)₂-promoted reactions with activated alkenes to give indanol products with higher specificity than similar Pd(II)- or Me₃NO-promoted reactions.